Nasal drug delivery 2

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Nasal drug delivery 2

  1. 1. NASAL DRUGDELIVERY SYSTEM 1
  2. 2. IntroductIon Intranasal Medication administration offers a truly“Needleless” solution to drug delivery.Therapy through intranasal administration has beenan accepted a form of treatment in the Ayurvedicsystem of Indian medicine 2
  3. 3. Merits 3
  4. 4. Limitations Once administered, rapid removal of the therapeutic agent from the site of absorption is difficult Pathologic conditions such as cold or allergies may alter significantly the nasal bioavailability 4
  5. 5. TE U L RO ts S A specN A a ic al ed-m 5
  6. 6. • The respiratory tract, which includes the – nasal mucosa – hypopharynx – large airways & – small airways• provides a relatively large mucosal surface area of approx. 100 m2 (in normal adult) for drug absorption 6
  7. 7. Cross-sectional viewNasal site of drug spray & absorptionPathways for nasal absorption 7
  8. 8. Cross-sectional viewa – nasal vestibule d – middle turbinateb – palate e – superior turbinate (olfactory mucosa)c – inferior turbinate f – nasopharynx 8
  9. 9. Site of drug spray &absorption 9
  10. 10. Pathways for nasal absorption Absorption through the olfactory neurons transneuronal absorption. Olfactory epithelium is considered as a portal for substances to enter CNS Absorption through the supporting cells & the surrounding capillary bed venous drainage Absorption into the cerebrospinal fluid 10
  11. 11. nose braIn pathway The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF. Medications absorbed across the olfactory mucosa directly enter the brain. This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain. Olfactory mucosa Brain CSF Highly vascular nasal mucosa 11
  12. 12. Nasal pH•Nasal secretion of adult : 5.5-6.5•Infants and children: 5-6.7•It becomes alkaline in conditions such as acute rhinitis, acute sinusitis.•Lysozyme in the nasal secretion helps as antibacterial and its activity is diminished in alkaline pH 12
  13. 13. of ss t e la u c ic l r o ut sa pe na r a or he s fT g dru 13
  14. 14. Therapeutic class of drugs 1. β2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 5. Antifungal 6. More recently, vaccines 14
  15. 15. Drugs commonly administered through pulmonary route include1. Terbutaline Sulphate - β2 adrenergic agonist2. Salbutamol - β2 adrenergic agonist3. Budesonide - corticosteroid4. Ipratropium Bromide - anticholinergic5. Sodium Chromoglycate – mast cell stabilizer 15
  16. 16. Formulation Development Dosage form Dosage form Factors affecting drug Factors affecting drug absorption absorption Formulation considerations Formulation considerations Physiological Pharmaceutical 16
  17. 17. Dosage forms Liquid drop Liquid spray/nebulizers AerosolSuspension spray/nebulizers Gel Sustained release 17
  18. 18. Drug concentrationFactors affecting pH of the absorption site drug absorption Size of the drug particle Relative lipid solubility Mucosal contact time Molecule weight of the drug 18
  19. 19. Factors Affecting BioavailabilityDelivery system characteristics:  Nasal mucosal surface area coverage: • Larger surface area delivery = higher bioavailability.  Particle size: • Particle size 10-50 microns adheres best to the nasal mucosa. • Smaller particles pass on to the lungs, larger particles form droplets and run-out of the nose. 19
  20. 20. cont..  Atomization results in higher bioavailability than either spray or drops.  For this reason, nasal pharmaceuticals come with atomized drug delivery systems. 20
  21. 21. Physiological effects- Drug metabolism in the respiratory tract & reduction of systemic effect- Protein binding- Mucociliary transport causing increased or decreased drug residence time 21
  22. 22. Physiological effects....- Local toxic effects of the drug Eg., edema, cell injury, or altered tissue defenses- Local or systemic effects of propellants, preservatives, or carriers 22
  23. 23. Methods to enhance nasal absorption of drugs Structural modification Salt or ester formation Formulation design 23
  24. 24. SPRAY PUMP DEVICES 24
  25. 25. BidoseMultidose Unidose 25
  26. 26. Nasal DropsNasal drops are one of the most simpleand convenient systems developed fornasal delivery.The main disadvantage of this system isthe lack of the dose precision andtherefore nasal drops may not be suitablefor prescription products.It has been reported that nasal dropsdeposit human serum albumin in thenostrils more efficiently than nasal sprays. 26
  27. 27. Nasal sprays Both solution and suspension formulations can be formulated into nasal sprays. Due to the availability of metered dose pumps and actuators, a nasal spray can deliver an exact dose from 25 to 200 μm. The particles size and morphology(for suspensions)of the drug and viscosity of the formulation determine the choice of pump and actuator assembly. 27
  28. 28. Lincoln Pharma wins patent for a novel nasal drug delivery system• Presently in India anti-vomiting treatments are available in the conventional form of tablet and injection which take longer time to bring relief.• But now through LPL’s new Nasal Drug Delivery System, the patient can get immediate relief. LPL becomes the first company in India to introduce an anti-vomiting treatment in the form of a Nasal spray pump.
  29. 29. • Stem Cell Nasal Spray for Parkinson Disease Significantly Improves Motor FunctionSuccessful intranasal delivery of stem cells to the brains ofrats with Parkinson disease yielded significantimprovement in motor function and reversed thedopamine deficiency characteristic of the disease.This was reported as a Rejuvenation Research in journalpublished by Mary Ann Liebert.
  30. 30. Mucosal Atomization Device (MAD)– Device designed to allow emergency personnel to delivery nasal medications as an atomized spray.– Broad 30-micron spray ensure excellent mucosal coverage.
  31. 31. Nasal PowderThis dosage form may be developed if solution andsuspension dosage forms cannot be developed e.g., due tolack of drug stability.The advantages to the nasal powder dosage form are theabsence of preservative and superior stability of theformulation.Local application of drug is another advantage of this system.Nasal powder formulation depends on the solubility,particles size, aerodynamic properties and nasal irritancy ofthe active drug and /or excipients. 31
  32. 32. Nasal GelsNasal gels are high-viscosity thickened solutions orsuspensions.Advantages of a nasal gelReduction of post-nasal drip due to high viscosity,Reduction of taste impact due to reduced swallowing,Reduction of anterior leakage of the formulation,Reduction of irritation by using soothing/emollientexcipients and target to mucosa for better absorption. 32
  33. 33. Nasal vaccinesNasal mucosa is first site of contact with inhaled antigensand, therefore, its use for vaccination, especially againstrespiratory infectionsNasal vaccination is a promising alternative to the classicparenteral route, because it is able to enhance the systemiclevels of specific immunoglobulin G and nasal secretaryimmunoglobulin A.Examples of human efficacy of intranasal vaccines includethose against influenza A and B virus, proteosoma influenza.Denovirusvectored influenza and parainfluenza virusIntra nasal H1N1 vaccine Nasovac by Serum Institute 33
  34. 34. Current systemic therapeutics deliverednasallyDesmopressin for diabetes mellitusCalcitonin for osteoporosisSumatriptan for migrainesNascobal for pernicious anemia
  35. 35. Nasal Drug Delivery medicationsDrugs of interest in Intranasal systems:  Intranasal naloxone (Narcan)  Intranasal midazolam (Versed) 35
  36. 36. Intranasal (IN) Naloxone Absorption of Intranasal naloxone almost as fast as IV in both animal and human models “Atomization” of medications show much better absorption via the Intranasal route 36
  37. 37. Examples of Intranasal Drug Delivery SystemsIntranasal sustained-release formulation – Nasal absorption with Clofilium tosylate, enkephalin analogs – Short biological half-lifeTobispray – Dry, metered-dose nasal aerosol – Vasoconstrictor (tramazoline), steroid (dexamethasone isonicotinate), antibiotic (neomycin sulfate)Other examples are : Butorphanol, calcitocin, sumatriptan, Insulin, Vaccine and brain targeting drugs. 37
  38. 38. Cont… Efficacy of cocaine by oral and intranasal administration – Nasal : detect in plasma by 15 min, peak concentration at 60 to 120 min, decrease gradually over the next 2 to 3h – Oral : not detected until 30 min, increased rapidly for the next 30 min In vivo absorption of sulbenicillin, cephacetrile, cephazoline – Oral : poor absorption because of high water solubility – Intranasal : ½ of im injection (% excretion in the urine ) 38
  39. 39. Market productotrivin spray (xylometazoline)miacalcin spray (calcitonin)vibrocil gel (phenylephrine,dimethindene maleate )naset-p (xylometazoline HCL)-nasal dropnasovac H1N1 vaccine 39
  40. 40. Leading pump suppliers 40
  41. 41. Applications Delivery of non-peptide pharmaceuticalsDelivery of peptide-based pharmaceuticals Delivery of diagnostic drugs 41
  42. 42. 1. Delivery of non-peptide pharmaceuticalsDrugs with extensive pre-systemic metabolism, such as- progesterone- estradiol- propranolol- nitroglycerin- sodium chromoglyatecan be rapidly absorbed through the nasal mucosawith a systemic bioavailability of approximately 100% 42
  43. 43. 2. Delivery of peptide-based pharmaceuticalsPeptides & proteins have a generally low oralbioavailability because of their physico-chemicalinstability and susceptibility to hepato-gastrointestinal first-pass eliminationEg. Insulin, Calcitonin, Pituitary hormones etc.Nasal route is proving to be the best route for suchbiotechnological products 43
  44. 44. 3. Delivery of diagnostic drugs Diagnostic agents such as • Phenolsulfonphthalein – kidney function • Secretin – pancreatic disorders • Pentagastrin – secretory function of gastric acid 44
  45. 45. 45

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